Sex difference in coronavirus disease (COVID-19): a systematic review and meta-analysis

ObjectiveTo assess the sex difference in the prevalence of COVID-19 confirmed cases.DesignSystematic review and meta-analysis.SettingPubMed, Cochrane Library and Google Scholar were searched for related information. The authors developed a data extraction form on an Excel sheet and the following data from eligible studies were extracted: author, country, sample size, number of female patients and number of male patients. Using STATA V.14 for analysis, the authors pooled the overall prevalence of men and/or women using a random-effect meta-analysis model. The authors examined the heterogeneity in effect size using Q statistics and I2 statistics. Subgroup and sensitivity analyses were performed. Publication bias was also checked.ParticipantsStudies on COVID-19 confirmed cases were included.InterventionSex (male/female) of COVID-19 confirmed cases was considered.Primary and secondary outcome measuresThe primary outcome was prevalence of COVID-19 among men and women.ResultsA total of 57 studies with 221 195 participants were used in the analysis. The pooled prevalence of COVID-19 among men was found to be 55.00 (51.43–56.58, I2=99.5%, p<0.001). Sensitivity analysis showed the findings were not dependent on a single study. Moreover, a funnel plot showed symmetrical distribution. Egger’s regression test p value was not significant, which indicates absence of publication bias in both outcomes.ConclusionsThe prevalence of symptomatic COVID-19 was found to be higher in men than in women. The high prevalence of smoking and alcohol consumption contributed to the high prevalence of COVID-19 among men. Additional studies on the discrepancies in severity and mortality rate due to COVID-19 among men and women and the associated factors are recommended.

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Global Incidence of Necrotizing Enterocolitis: a Systematic Review and Meta-Analysis

10.21203/rs.3.rs-17868/v2 ◽

2020 ◽

Author(s):

Amer Alsaied ◽

Nazmul Islam ◽

Lukman Thalib

Keyword(s):

Systematic Review ◽

Cohort Studies ◽

Publication Bias ◽

Necrotizing Enterocolitis ◽

Meta Analysis ◽

Sensitivity Analyses ◽

Cochrane Library ◽

Vlbw Infants ◽

Funnel Plots ◽

Substantial Heterogeneity

Abstract Background: Necrotizing Enterocolitis (NEC) is a major cause of morbidity and mortality in the Neonatal Intensive Care Unit (NICU), yet the global incidence of NEC has not been systematically evaluated. We conducted a systematic review and meta-analysis of cohort studies reporting the incidence of NEC in infants with Very Low Birth Weight (VLBW).Methods: The databases searched included PubMed, MEDLINE, the Cochrane Library, EMBASE and grey literature. Eligible studies were cohort or population-based studies of newborns including registry data reporting incidence of NEC. Data were extracted from the selected papers included incidence of NEC cases and size of population at risk, author and publication details, follow up period covered by the study, location and setting of the study and whether it was VLBW infants or preterm infants. Additionally, risk of bias assessment of the included studies were carried out using a validated tool. Bias adjusted Quality Effect Model (QEM) were used to pool the estimates. In the presence of substantial heterogeneity, Random Effect Models (REM) were used as an additionally sensitivity analyses. The heterogeneity between studies were evaluated using the Cochrane Q statistics and Higgin’s I2 value. Subgroup analysis and meta-regression were used to explore the sources of heterogeneity. Funnel plots as appropriate for ratio measures were used to assess publication bias. Results: A systematic and comprehensive search of databases identified 27 cohort studies reporting the incidence of NEC. The pooled estimate of the global incidence of NEC was 6.0% (95% CI: 4.0%-9.0%). There were substantial heterogeneity (I2 = 100%) between studies. Funnel plots showed no evidence of publication bias.Conclusion: Seven out of 100 of all VLBW infants in NICU are likely to develop NEC. However, there were considerable heterogeneity between studies. High quality studies assessing incidence of NEC along with associated risk factors are warranted.

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Optimal cut-off value of elevated cardiac troponin concentrations for myocardial injury predicts clinical outcomes in adult patients with COVID-19: a dose–response analysis protocol for systematic review

BMJ Open ◽

10.1136/bmjopen-2020-046575 ◽

2021 ◽

Vol 11 (1) ◽

pp. e046575

Author(s):

Chenghui Zhou ◽

Hanjun Pei ◽

Yiming Gao ◽

Yulin Zhang ◽

Liang Cao ◽

...

Keyword(s):

Systematic Review ◽

Clinical Outcomes ◽

Dose Response ◽

Cardiac Troponin ◽

Myocardial Injury ◽

Meta Analysis ◽

Sensitivity Analyses ◽

Cochrane Library ◽

Secondary Outcome ◽

All Cause Mortality

IntroductionAcute myocardial injury in patients with COVID-19 infection has been recognised as one important complication associated with in-hospital mortality. The potential dose–response effect of cardiac troponin (cTn) concentrations on adverse clinical outcomes has not been systematically studied. Hence, we will conduct a comprehensive dose–response meta-analysis to quantitatively evaluate the relationship between elevated cTn concentrations and in-hospital adverse clinical outcomes in patients with COVID-19.MethodsWe will search PubMed, EMBASE, Cochrane Library and ISI Knowledge via Web of Science databases, as well as preprint databases (medRxiv and bioRxiv), from inception to October 2021, to identify all retrospective and prospective cohorts and randomised controlled studies using related keywords. The primary outcome will be all-cause mortality during hospitalisation. The secondary outcome will be major adverse event (MAE). To conduct a dose–response meta-analysis of the potential linear or restricted cubic spline regression relationship between elevated cTn concentrations and all-cause mortality or MAE, studies with three or more categories of cTn concentrations will be included. Univariable or multivariable meta-regression and subgroup analyses will be conducted to compare elevated and non-elevated categories of cTn concentration. Sensitivity analyses will be used to assess the robustness of our results by removing each included study at one time to obtain and evaluate the remaining overall estimates of all-cause mortality or MAE.Ethics and disseminationIn accordance with the Institutional Review Board/Independent Ethics Committee of Fuwai Hospital, ethical approval was waived for this systematic review protocol. This meta-analysis will be disseminated through a peer-reviewing process for journal publication and conference communication.PROSPERO registration numberCRD42020216059.

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Effect of garlic intake on inflammatory mediators: a systematic review and meta-analysis of randomised controlled trials

Postgraduate Medical Journal ◽

10.1136/postgradmedj-2019-137267 ◽

2020 ◽

pp. postgradmedj-2019-137267

Author(s):

Mehdi Koushki ◽

Nasrin Amiri-Dashatan ◽

Yasin Pourfarjam ◽

Amir Hossein Doustimotlagh

Keyword(s):

Systematic Review ◽

Inflammatory Mediators ◽

Metabolic Diseases ◽

Meta Analysis ◽

Random Effect ◽

Sensitivity Analyses ◽

Current Evidence ◽

Cochrane Library ◽

Tnf Α ◽

The Impact

BackgroundGarlic is a species in the onion genus, Allium. Data have shown that garlic has anti-inflammatory activity; however, the findings are inconclusive and inconsistent. We aimed to evaluate the impact of garlic intake on inflammatory mediators through systematic review and meta-analysis of existing data.MethodsElectronic databases were completely investigated using databases of ISI Web of Science, Medline, Scopus, Cochrane Library and EMBASE until October 2019. A random effects model and the generic reverse variance procedure were used for quantitative data production. Sensitivity analyses and prespecified subgroup were done to evaluate potential heterogeneity. Random effect meta-regression was conducted to investigate the effects of possible confounders on the assessed effect size.ResultsTen trials with one observational study, including 530 participants, met the eligibility criteria. The findings showed reduction in the tumour necrosis factor alpha (TNF-α) (−0.31 pg/mL, 95% CI −1.07 to 0.46) and C reactive protein (CRP) levels (−0.20 mg/L, 95% CI −1.4 to 1.05) following supplementation with garlic, although it had no marked impact on the interleukin 6 (IL-6) level (0.37 pg/mL, 95% CI −0.58 to 1.33). In the subgroup analysis, we found that garlic supplementation significantly decreased TNF-α, highly sensitive CRP and IL-6 levels in subgroups of >8, >6 and ≥4 weeks of intervention duration, respectively, and dose of garlic consumption between 2 and 2.4 g/day.ConclusionThese findings suggested that current evidence may support garlic as an adjunct to pharmacological management of metabolic diseases.PROSPERO registration numberCRD42018108816.

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Palivizumab and prevention of childhood respiratory syncytial viral infection: protocol for a systematic review and meta-analysis of breakthrough infections

BMJ Open ◽

10.1136/bmjopen-2019-029832 ◽

2019 ◽

Vol 9 (7) ◽

pp. e029832

Author(s):

Shelly Jun ◽

Meghan Sebastianski ◽

Robin Featherstone ◽

Joan Robinson

Keyword(s):

Systematic Review ◽

Vaccine Development ◽

Meta Analysis ◽

Respiratory Illness ◽

Sensitivity Analyses ◽

Cochrane Library ◽

Secondary Outcome ◽

New Findings ◽

Rsv Infection ◽

Syncytial Virus

IntroductionChildhood respiratory syncytial virus (RSV) infection is a global phenomenon that can lead to fatal respiratory illness. Palivizumab is a drug that is routinely used in affluent countries as a prophylaxis against RSV infection; nevertheless, breakthrough infections are often reported. In light of new findings on potential RSV resistance to palivizumab, an up-to-date synthesis of evidence on effectiveness is needed. Furthering existing reviews, a broadened scope to better reflect effectiveness in a ‘real world’ clinical context is also important. This systematic review and meta-analysis will enhance our understanding of the effectiveness of palivizumab in varying populations of children. Findings from this review will inform recommendations for best practices regarding palivizumab use for childhood RSV infection as well as research priorities in RSV vaccine development.Methods and analysisWe will conduct a systematic review of primary population-based studies that examine the incidence of palivizumab breakthrough infections in children, published between 1997 to present. In collaboration with a research librarian, four electronic databases (MEDLINE, Embase, Cochrane Library, Web of Science) and additional sources will be searched. Study screening and quality assessment will be performed in duplicate. Data will be extracted by one reviewer, with partial and random verification by a second reviewer. The primary outcomes to assess breakthrough RSV infection will be hospitalisation, length of stay and the need for intensive care unit admission and mechanical ventilation in children receiving palivizumab. The secondary outcome will be RSV-associated mortality. We will conduct a meta-analysis using pooled effectiveness data, and include subgroup analyses by patient comorbidities and drug compliance. Sensitivity analyses for risk of bias and study design will also be performed.Ethics and disseminationThis systematic review will only include data from previously published literature and is therefore exempt from ethics approval. Final results will be disseminated through peer-reviewed publication and presented at academic conferences and scientific meetings engaging paediatric researchers and healthcare providers. Should findings from this review necessitate updates to current clinical practice guidelines, we intend to establish a working group to engage relevant health administrators and decision makers.PROSPERO registration numberCRD42019122120.

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Secondhand smoke exposure and oral cancer risk: a systematic review and meta-analysis

Tobacco Control ◽

10.1136/tobaccocontrol-2020-056393 ◽

2021 ◽

pp. tobaccocontrol-2020-056393

Author(s):

Lorena C. Mariano ◽

Saman Warnakulasuryia ◽

Kurt Straif ◽

Luís Monteiro

Keyword(s):

Systematic Review ◽

Oral Cancer ◽

Secondhand Smoke ◽

Meta Analysis ◽

Random Effect ◽

Sensitivity Analyses ◽

Cochrane Library ◽

Significant Heterogeneity ◽

Eligibility Criteria ◽

Shs Exposure

ObjectivesInhalation of secondhand smoke (SHS) causes several diseases, including lung cancer. Tobacco smoking is a known cause of oral cancer; however, it has not been established whether SHS also causes oral cancer . The aim of this study was to evaluate the potential association between SHS exposure and the risk of oral cancer.MethodsA systematic review and meta-analysis study (following the PRISMA guidelines) was developed to examine the studies reporting on the associations of SHS and the risk of oral cancer, employing a search strategy on electronic databases (PubMed, Web of Science, Scopus, Cochrane Library, Open Grey, and ProQuest databases for dissertations) until 10 May 2020. Meta-analyses and sensitivity analyses were performed using random-effect models. The protocol was registered in PROSPERO (CRD42020189970).ResultsFollowing the application of eligibility criteria, five studies were included, comprising a total of 1179 cases and 5798 controls, with 3452 individuals exposed and 3525 individuals not exposed to SHS. An overall OR of 1.51 (95% CI 1.2o to 1.91, p=0.0004) for oral cancer was observed, without significant heterogeneity (I2=0%, p=0.41). The duration of exposure of more than 10 or 15 years increased the risk of oral cancer (OR 2.07, 95% CI 1.54 to 2.79, p<0.00001), compared with non-exposed individuals, without significant heterogeneity (I2=0%, p=0.76).ConclusionsThis systematic review and meta-analysis supports a causal association between SHS exposure and oral cancer. Our results could provide guidance to public health professionals, researchers, and policymakers to further support effective SHS exposure prevention programs worldwide.

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Systematic review and meta-analysis of the prevalence of depressive symptoms, dysthymia and major depressive disorders among homeless people

BMJ Open ◽

10.1136/bmjopen-2020-040061 ◽

2021 ◽

Vol 11 (2) ◽

pp. e040061

Author(s):

Getinet Ayano ◽

Asmare Belete ◽

Bereket Duko ◽

Light Tsegay ◽

Berihun Assefa Dachew

Keyword(s):

Systematic Review ◽

Depressive Symptoms ◽

Depressive Disorders ◽

Meta Analysis ◽

Random Effect ◽

Homeless People ◽

Sensitivity Analyses ◽

Prevalence Rates ◽

Major Depressive ◽

Major Depressive Disorders

ObjectivesTo assess the global prevalence estimates of depressive symptoms, dysthymia and major depressive disorders (MDDs) among homeless people.DesignSystematic review and meta-analysis.Data sourcesDatabases including PubMed, Scopus and Web of Science were systematically searched up to February 2020 to identify relevant studies that have reported data on the prevalence of depressive symptoms, dysthymia and MDDs among homeless people.Eligibility criteriaOriginal epidemiological studies written in English that addressed the prevalence of depressive problems among homeless people.Data extraction and synthesisA random-effect meta-analysis was performed to pool the prevalence estimated from individual studies. Subgroup and sensitivity analyses were employed to compare the prevalence across the groups as well as to identify the source of heterogeneities. The Joanna Briggs Institute’s quality assessment checklist was used to measure the study quality. Cochran’s Q and the I2 test were used to assess heterogeneity between the studies.ResultsForty publications, including 17 215 participants, were included in the final analysis. This meta-analysis demonstrated considerably higher prevalence rates of depressive symptoms 46.72% (95% CI 37.77% to 55.90%), dysthymia 8.25% (95% CI 4.79% to 11.86%), as well as MDDs 26.24% (95% CI 21.02% to 32.22%) among homeless people. Our subgroup analysis showed that the prevalence of depressive symptoms was high among younger homeless people (<25 years of age), whereas the prevalence of MDD was high among older homeless people (>50 years of age) when compared with adults (25–50 years).ConclusionThis review showed that nearly half, one-fourth and one-tenth of homeless people are suffering from depressive symptoms, dysthymia and MDDs, respectively, which are notably higher than the reported prevalence rates in the general population. The findings suggest the need for appropriate mental health prevention and treatment strategies for this population group.

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Mindfulness-based and acceptance-based programmes in the treatment of obsessive–compulsive disorder: a study protocol for a systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2021-050329 ◽

2021 ◽

Vol 11 (6) ◽

pp. e050329

Author(s):

Johannes Julian Bürkle ◽

Johannes Caspar Fendel ◽

Stefan Schmidt

Keyword(s):

Systematic Review ◽

Depressive Symptoms ◽

Obsessive Compulsive Disorder ◽

Meta Analysis ◽

Sensitivity Analyses ◽

Secondary Outcome ◽

Controlled Trials ◽

Obsessive Compulsive ◽

Compulsive Disorder

IntroductionCognitive–behavioural therapy (CBT) with exposure and response prevention is the recommended standard for the treatment of obsessive–compulsive disorder (OCD). However, a high proportion of patients refuse this treatment, do not respond or relapse shortly after treatment. Growing evidence suggests that mindfulness-based and acceptance-based programmes (MABPs) are an effective option for the treatment of OCD. This systematic review and meta-analysis will examine the effectiveness of MABPs in treating OCD. We also aimed to explore potential moderators of the programmes’ effectiveness.Methods and analysisWe will systematically search MEDLINE, Embase, PsycINFO, PSYINDEX, Web of Science, CINAHL and Cochrane Register of Controlled Trials (no language restrictions) for studies that evaluate the effect of MABPs on patients with OCD. We will conduct backward and forward citation searches of included studies and relevant reviews and contact corresponding authors. The primary outcome will be pre-post intervention change in symptom severity. A secondary outcome will be change in depressive symptoms. Two reviewers will independently screen the records, extract the data and rate the methodological quality of the studies. We will include both controlled and uncontrolled trials. Randomised controlled trials will be meta-analysed, separately assessing between-group effects. A second meta-analysis will assess the within-group effect of all eligible studies. We will explore moderators and sources of heterogeneity such as the specific programme, study design, changes in depressive symptoms, hours of guided treatment, control condition and prior therapy (eg, CBT) using metaregression and subgroup analyses. We will perform sensitivity analyses using follow-up data. A narrative synthesis will also be pursued. We will use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to assess the quality of the evidence.Ethics and disseminationEthical approval is not required. Results will be published in peer-reviewed journals and presented at international conferences.

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Efficacy and safety of anti-epidermal growth factor receptor agents for the treatment of oesophageal cancer: a systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2020-046352 ◽

2021 ◽

Vol 11 (3) ◽

pp. e046352

Author(s):

Lijuan Zhang ◽

Yanli Song ◽

Nan Jiang ◽

Yaqi Huang ◽

Bo Dong ◽

...

Keyword(s):

Systematic Review ◽

Growth Factor ◽

Outcome Measures ◽

Oesophageal Cancer ◽

Meta Analysis ◽

Growth Factor Receptor ◽

Cochrane Library ◽

Secondary Outcome ◽

Efficacy And Safety ◽

Positive Effects

ObjectivesDespite remarkable advances in the treatment of oesophageal cancer (OC), the role of antiepidermal growth factor receptor (anti-EGFR) agents in treating OC remains controversial. Herein, a systematic review and meta-analysis were conducted to elucidate the efficacy and safety of anti-EGFR agents in patients with OC.DesignMeta-analysis of randomised controlled trials (RCTs) identified by searching the PubMed, Embase, Web of Science, ClinicalTrials.gov, Cochrane Library, Chinese Biology Medicine, China National Knowledge Infrastructure and Wanfang Data Knowledge Service Platform databases from inception to December 2019. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.SettingRCTs from any country and healthcare setting.ParticipantsPatients with OC.InterventionsCombination therapy with anti-EGFR agents and conventional treatments versus conventional treatments alone in patients with OC.Primary and secondary outcome measuresOverall survival (OS) and progression-free survival (PFS) were primary outcome measures, and objective response rate (ORR), disease control rate (DCR) and treatment toxicities were secondary outcome measures.ResultsIn total, 25 RCTs comprising 3406 patients with OC were included. Overall, anti-EGFR treatment significantly improved the OS (HR: 0.81, 95% CI 0.74 to 0.89, p<0.00001), ORR (relative risk (RR): 1.33, 95% CI 1.16 to 1.52, p<0.0001) and DCR (RR: 1.22, 95% CI 1.11 to 1.34, p<0.0001) but not PFS (HR: 0.91, 95% CI 0.76 to 1.08, p=0.26). Anti-EGFR treatment was significantly associated with higher incidences of myelosuppression, diarrhoea, acne-like rash and hypomagnesaemia.ConclusionsOverall, anti-EGFR agents have positive effects on OS, the ORR and DCR in OC. However, considering the high incidence of adverse effects, such as myelosuppression, diarrhoea, acne-like rashes and hypomagnesaemia, careful monitoring of patients with OC is recommended during anti-EGFR treatment.Trial registration numberCRD42020169230.

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Risk of dementia in gout and hyperuricaemia: a meta-analysis of cohort studies

BMJ Open ◽

10.1136/bmjopen-2020-041680 ◽

2021 ◽

Vol 11 (6) ◽

pp. e041680

Author(s):

Shu-Yue Pan ◽

Rui-Juan Cheng ◽

Zi-Jing Xia ◽

Qiu-Ping Zhang ◽

Yi Liu

Keyword(s):

Cohort Studies ◽

Quality Assessment ◽

Publication Bias ◽

Data Extraction ◽

Meta Analysis ◽

Sensitivity Analyses ◽

Cochrane Library ◽

Crystal Formation ◽

Medical Subject Headings ◽

Eligibility Criteria

ObjectivesGout, characterised by hyperuricaemia with monosodium urate crystal formation and inflammation, is the most common inflammatory arthritis in adults. Recent studies have found that elevated uric acid levels are related to the occurrence of dementia. We conducted a study to investigate the association between dementia and gout or hyperuricaemia.DesignSystematic review and meta-analysis of cohort studies.Data sourcesStudies were screened from inception to 28 June 2019 by searching Medline, Embase and the Cochrane Library databases.Eligibility criteriaCohort studies comparing the risk of dementia in patients with gout and hyperuricaemia versus non-gout and non-hyperuricaemia controls were enrolled.Data extraction and analysisTwo reviewers separately selected studies and extracted data using the Medical Subject Headings without restriction on languages or countries. The adjusted HRs were pooled using the DerSimonian and Laird random effects model. Sensitivity analyses were conducted to evaluate the stability of the results. Publication bias was evaluated using Egger’s and Begg’s tests. Quality assessment was performed according to the Newcastle-Ottawa Scale.ResultsFour cohort studies that met the inclusion criteria were included in our meta-analysis. We found that gout and hyperuricaemia did not increase the risk of dementia, with a pooled HR of 0.94 (95% CI 0.69 to 1.28), but might decrease the risk of Alzheimer’s disease (AD), with a pooled HR of 0.78 (95% CI 0.64 to 0.95). There was little evidence of publication bias. Quality assessment of the included studies was high (range: 6–8 points).ConclusionsOur study shows that gout and hyperuricaemia do not increase the risk of dementia. However, gout and hyperuricaemia might have a protective effect against AD. Due to the limited number of research articles, more investigations are needed to demonstrate the potential relationship between dementia and gout or hyperuricaemia.

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Association between Oral Contraceptives and cutaneous melanoma: a systematic review and metanalysis

European Journal of Public Health ◽

10.1093/eurpub/ckaa166.1093 ◽

2020 ◽

Vol 30 (Supplement_5) ◽

Author(s):

I Giacchetta ◽

M Chiavarini ◽

G Naldini ◽

R Fabiani

Keyword(s):

Systematic Review ◽

Malignant Melanoma ◽

Publication Bias ◽

Oral Contraceptives ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Cutaneous Malignant Melanoma ◽

Hormonal Factors ◽

Increased Risk

Abstract Background The probability of developing invasive cutaneous malignant melanoma (CMM) is higher in women than in men up until the age of 49. Several studies investigated the association between hormonal factors and CMM. The aim of this systematic review and meta-analysis is to summarize the evidence on the association between Oral Contraceptives (OC) and the risk of CMM. Methods This review and meta-analysis follow the PRISMA guidelines. A systematic literature search was conducted on Medline and Web of Science until December 2019. Studies were eligible if reported a risk estimate for the association between OC and CMM. Heterogeneity testing was performed using Cochran's Q and I2 statistics. Publication bias was assessed by Egger's test and Begg's test. Meta-analysis was performed using random effect model. Results The results of the pooled analysis of all 32 studies showed no significant association between OC and the risk of CMM (OR 1.02; 95% CI 0.94-1.11; I2=39.32%, p = 0.013). The stratified analyses by study design found no significant association between OC and the risk of CMM neither in the 18 case-control studies (OR 1.02; 95% CI 0.87-1.21; I2=56.91%, p = 0.002) nor in the 14 cohort studies (OR 1.04; 95% CI 0.98-1.11; I2=0.00%, p = 0.557). No significant publication bias could be detected by Egger's test or Begg's test. Conclusions This meta-analysis of available literature suggests no significant association between OC and the risk of developing CMM. Further investigations are needed to evaluate the possible relationship of OC use and other hormonal factors potentially contributing to the increased risk of CMM in women during their reproductive years. Key messages Oral contraceptives (OC) do not significantly contribute to the risk of Cutaneous Malignant Melanoma (CMM). Further studies are needed to investigate the potential role of other hormonal factors in the increased probability of developing CMM in women during their reproductive years.

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